SYK-DEPENDENT AND SYK-INDEPENDENT SIGNALING CASCADES IN B-CELLS ELICITED BY OSMOTIC AND OXIDATIVE STRESS

It was found that Syk protein-tyrosine kinase is rapidly activated in B cells after H2O2 treatment (oxidative stress) or increased extracell ular NaCI concentration (osmotic stress) as well as in response to B c ell receptor activation. In this study we examined the involvement of Syk in responses elicited by these types of extracellular stress, part icularly Ca2+ responses and c-Jun aminoterminal kinase (JPK) activatio n, using a chicken B cell line, DT40, as well as the DT40-derived muta nt DT40/Syk(-), which does not express Syk. Osmotic stress evokes incr eases in [Ca2+](i) by stimulating an extracellular Ca2+ influx in both DT40 and DT40/Syk(-) cells. In comparison, oxidative stress elicits a n increase in [Ca2+](i) by stimulating both an extracellular Ca2+ infl ux and Ca2+ release from internal stores in DT40 cells, but this Ca2response is partially abolished in DT40/Syk(-) cells, indicating that the oxidative stress-induced Ca2+ response is at least partly dependen t on Syk. Interestingly, the depletion of Ca2+ results in a significan tly decreased level of Syk activation in DT40 cells stimulated by oxid ative but not osmotic stress. Furthermore, JNK is activated to differe nt extents by these two types of stress. The extent of JNK activation in DT40/Syk(-) cells in response to osmotic stress is comparable to th at observed in DT40 cells. Intriguingly, oxidative stress-induced JNK activation is significantly compromised in DT40/Syk(-) cells. Collecti vely, these results indicate that both the Ca2+ response and JNK. acti vity induced by oxidative stress are partly dependent on Syk, whereas those induced by osmotic stress are independent of Syk.